High discordance rate in assessing sentinel node positivity in cutaneous melanoma: Expert review may reduce unjustified adjuvant treatment
El Sharouni, Mary Ann; Laeijendecker, Annelien E.; Suijkerbuijk, Karijn PM; Witkamp, Arjen J.; Sigurdsson, Vigfús; van Diest, Paul J.; van Gils, Carla H.; Blokx, Willeke AM
(2021) European Journal of Cancer, volume 149, pp. 105 - 113
(Article)
Abstract
Introduction: Identification of sentinel node (SN) metastases can set the adjuvant systemic therapy indication for patients with stage III melanoma. Studies re-evaluating the diagnosis of initially positive SN biopsies are scarce. Materials and methods: Dutch patients with melanoma who underwent SN biopsy between 2003 and 2014 were selected from PALGA,
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the Dutch Pathology Registry. Histopathological slides of SN-positive patients were retrieved for review. A random sample was reassessed by an expert melanoma pathologist. Recurrence-free survival (RFS) of patients who were misclassified (false-positive) was compared with those with a true positive SN status. For comparison, a group of SN-negative patients was included. Multivariable logistic analysis was performed to assess clinicopathological characteristics associated with misclassification of SN status. Results: Diagnosis was downgraded from melanoma metastasis to nodal nevus in 38 of the 322 reviewed patients (11.8%). Considering the inclusion criteria of phase III adjuvant trials, at least 4.3% of patients would have falsely qualified for adjuvant therapy. In multivariable analysis, patients with a low SN tumour burden and subcapsular SN tumour location had a significantly higher chance of being misclassified. The five-year RFS of the 38 downgraded patients was 86.7% (95% confidence interval [CI] = 72.6–96.6), similar to the 85.9% (95% CI = 84.9–86.8, p = 0.18) for 6413 SN-negative patients and better than the 53.2% (95% CI = 47.2–59.9, p = 0.009) of 284 patients who were truly SN positive upon review. Conclusion: More than 10% of originally positive SN biopsies of patients with melanoma concern misclassified nodal nevi. We advocate that when adjuvant treatment is considered in patients with stage III melanoma, SN biopsies should be reassessed by an expert melanoma pathologist.
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Keywords: Adjuvant therapy, Melanoma, Nodal nevus, Pathology, Sentinel, Predictive Value of Tests, Humans, Middle Aged, Male, Unnecessary Procedures, False Positive Reactions, Patient Selection, Netherlands, Clinical Decision-Making, Adult, Female, Registries, Sentinel Lymph Node/pathology, Retrospective Studies, Melanoma/secondary, Reproducibility of Results, Treatment Outcome, Combined Modality Therapy, Skin Neoplasms/pathology, Aged, Sentinel Lymph Node Biopsy, Neoplasm Staging, Observer Variation, Oncology, Cancer Research, Journal Article
ISSN: 0959-8049
Publisher: Elsevier Limited
Note: Funding Information: The authors thank Rinus Voorham (PALGA, the Dutch Pathology Registry) for his assistance with data extraction, all the pathology laboratories that participated in our study and all their pathology employees for their efforts in retrieving the slides. The authors thank Nikolas Stathonikos (University Medical Center Utrecht) for his help with digitalizing the histopathological slides. Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved. Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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